Method for inducing onset of the reproductive cycle of female breeding animals

ABSTRACT

A method for inducing the onset of the reproductive cycle of female breeding animals is provided. To this end, the animals are injected with an agent that contains synthetically produced FSH releasing hormones as the active substance which comprise known sequences, consisting of 10 amino acids (decapeptide). The active substances are administered to the animals in the form of solution 0 to 96 hours after termination of the preceding anestrus or inhibition or a biotechnical treatment. The agents used promote an onset of the reproductive cycle after the young animals have been weaned from the mature animals and a synchronization of heat in animals that are to be inseminated for the first time.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a National Phase Patent Application of InternationalApplication Number PCT/DE01/03870, filed on Oct. 5, 2001, which claimspriority of German Patent Application Number 100 50 831.6, filed Oct. 5,2000.

FIELD OF THE INVENTION

The invention relates to a method for inducing the onset of thereproductive cycle of female breeding animals.

In the business and commercial sector of livestock breeding and in theproduction of litters, group farrowing is increasingly practiced. Inconjunction with the widespread use of artificial insemination, there isthe essential prerequisite of being able to supply large litters ofmarket quality that are uniformly healthy.

At the same time, interest is increasing in suitable biotechnicalmethods to control the individual reproductive cycles within thecombined group of animals.

The hormone systems directly involved in reproduction operate in a largeregulatory cycle of neuroendocrine integration. This produces thehormonal prerequisites for the course of the heat cycle. Naturally,after the end of sexual activity, e.g., after anestrus in cyclicalanimals, after weaning and separation of the mothers from the younganimals or after previous cycle inhibition, particularly under theinfluence of follicle stimulating hormones, the onset of follicle growthin the ovaries, followed by follicle ripening, onset of heat, ovulation,and possible fertilization in the event of timely insemination with afertile sperm. The individual cycles are subject to considerablebiological fluctuation. In livestock breeding, and in particular, inlitter production operations with a periodic removal of farrows, therearises, for reasons of economy and animal health, interest in narrowlylimited time periods for the most important reproductive events, i.e.,insemination and farrowing. The targeted control of follicle growth andsubsequent stages in groups of animals, e.g., weaned mature animals orgilts ready for first breeding, is used for the scheduled alignment ofbiological processes with necessary and desirable cycles in animalproduction.

Methods of cycle synchronization and influencing the reproductionfunctions have been developed in a variety of forms in recent years.They are based on the pharmacological possibilities of biotechnicalreproduction control.

In sow management, for example, it is known to induce heat byadministration of hormones. For a long time, cycle-appropriate use ofgonadotropic hormone preparations of natural origin following apreceding cycle inhibition, e.g., through lactation in mature animalsand heat synchronization through medication in gilts, has beenconsidered.

The use of pregnant mare serum gonadotropin PMSG is known. PMSG isobtained from pregnant mares using the Aderlass method. Animalprotection objections against this are increasing. Also, the use ofcertain PMSG lots, in particular those preserved in liquid form,contribute to adverse side effects, e.g., anaphylactic shock reactions.

DESCRIPTION OF THE INVENTION

The invention is directed to methods for inducing the onset of thereproductive cycle for breeding animals that is adapted to the naturalbiological course of the sexual cycle and causes scheduled control ofthe onset of follicle growth in the ovaries as well as the onset of heatin a group of breeding animals.

In an exemplary embodiment, the invention is directed to a method toinduce the onset of the reproductive cycle in breeding animals, whereinan agent is used that includes as its active substance syntheticallyproduced FSH-releasing hormones with known sequences comprising 10 aminoacids (decapeptide) in addition to the usual adjuvants. The decapeptidementioned has the amino acid sequencePyr-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH₂. This sequence can bemodified by the addition of further components.

It has been determined that a specific injection in animals previouslyin anestrus causes scheduled control of the beginning follicle growth inthe ovaries. This produces, as onset of the reproductive cycle, theprerequisite for synchronization of follicle ripening, secretion of theheat hormone and the start of estrus in the treated animals. The effectis based both on the stimulation of functions of the anterior lobe ofthe pituitary gland as well as the ovaries, whereby a number of oocytesfrom the latent pool of the follicle population within or in excess ofphysiological limits simultaneously enter the growth phase. This effectis used for the subsequent breeding, primarily artificial insemination.

In the method according to the invention, quantities from about 5 μg toabout 500 μg active substance per milliliter of injection solution areused. Preferably, the active substance quantities are from about 50 toabout 300 μg and, more preferably, about 100 to about 200 μg permilliliter of injection liquid.

A suitable use variant comprises aqueous solutions that may containfurther customary adjuvants in addition to the active substance.

Per animal, quantities of about 20 to about 500 μg, preferably about 50to about 300 μg, and, more preferably, about 100 to about 200 μg ofactive substances are administered to each animal with each injection.

The administration of the injection solution takes place in a period of0 to 96 hours, preferably 12 to 48 hours, and, more particularly, 24hours after the end of a previous anestrous or cycle inhibition or abiotechnical pretreatment.

Appropriate administrations of the agent in the method according to theinvention and its modifications in breeding animals are possible bymeans of implanted osmotic pumps, by multiple injection, as asustained-release preparation or as an infusion with sustained-releaseaction. Use as a sustained-release preparation yields the advantage thatwith one-time administration of the preparation the quantity of activesubstance for the triggering of the desired onset of the reproductivecycle was administered to the animals. This contributes significantly tostress reduction

With the method according to the invention, a practical method to inducethe onset of the reproductive cycle in breeding animals managed ingroups is available. Advantageous results have been obtained in breedingsows managed in groups.

The invention is illustrated in detail in the following exemplaryembodiment.

After the end of a four-week lactation, farrows were separated frombreeding sows. 24 hours after separation, an injection solution thatcontains 125 μg active substance is administered per animal to thebreeding sows to induce the onset of the reproductive cycle.

If receptivity-based insemination is planned, a verification of estrusinduced by the stimulated follicles and their estrogen production iscarried out. One to three inseminations are performed per estrus.

If time-based insemination is planned, an ovulation-triggering injectionwith an injection solution that contains D-Phe ⁶-Gonadorelin as activesubstance takes place at an interval of 72 hours after the injectionthat stimulates follicle growth.

The insemination takes place according to schedule. The firstinsemination is performed 24 to 26 hours after the ovulation-triggeringinjection and the second insemination takes place no later than 18 hoursthereafter.

1. A method for inducing onset of estrous of a sow after weaning andseparation of the sow from her piglets or after a previous inhibition ofthe estrous cycle, comprising injecting the sow with an injectionsolution that contains as an active substance a synthetically producedhormone comprising the decapeptide Pyr-HisTrp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH₂, whereby the decapeptide selectivelyreleases FSH without releasing LH.
 2. A method according to claim 1wherein the decapeptide solution is modified by the addition of furthercomponents.
 3. A method according to claim 1 wherein the activesubstance is injected 0 to 96 hours after weaning or the end of apreceding inhibition of the estrous cycle.
 4. A method according toclaim 1, wherein the injection solution contains from 5 to 500 μg ofactive substance per milliliter of injection solution.
 5. A methodaccording to claim 1, wherein the injection solution administered persow contains from 25 to 500 μg of active substance.
 6. A methodaccording to claim 1, further comprising administering anovulation-triggering injection comprising as an active substanceD-Phe⁶-Gonadorelin.
 7. A method according to claim 1, wherein the activesubstance is injected 12 to 48 hours after weaning or the end of apreceding inhibition of the estrous cycle.
 8. A method according toclaim 1, wherein the active substance is injected 24 hours after weaningor the end of a preceding inhibition of the estrous cycle.
 9. A methodaccording to claim 1, wherein the injection solution contains from 50 to300 μg of active substance per milliliter of injection solution.
 10. Amethod according to claim 1, wherein the injection solution containsfrom 100 to 200 μg of active substance per milliliter of injectionsolution.
 11. A method according to claim 1, wherein the total injectionsolution administered to the sow contains 50 to 300 μg of activesubstance.
 12. A method according to claim 1, wherein the totalinjection solution administered to the sow contains 100 to 200 μg ofactive substance.
 13. A method according to claim 6, wherein theovulation-triggering injection is administered after the injectionsolution is injected.
 14. A method according to claim 13, wherein theovulation-triggering injection is administered at least 72 hours afterthe injection solution is injected.
 15. A method according to claim 1,wherein the increase in FSH causes follicle growth and increasedestrogen production, increasing the LH level and thereby causingovulation.